Alpha Globulin is a rat liver protein whose synthesis is modulated by several hormones. A cloned alpha 2u globulin cDNA has been prepared and will be used to screen a rat genome library to isolate the chromosomal gene(s) coding for this protein. The purified alpha 2u globulin gene can then be stably introduced into cultured mammalian cells using a process known as cotransformation, and the hormonal inducibility of the transfered alpha 2u globulin gene will be determined. The alpha globulin gene and/or its flanking sequences will be specifically modified using site specific mutagenesis or using restriction enzymes to generate deletions. These mutant alpha 2u globulin genes will be introduced into cultured cells, and the effects of the mutations on the hormonal modulation will be assessed. Thus it may be possible to identify genomic sequences in or around the alpha 2u globulin gene which are involved in the multihormonal control of its synthesis.